Chlamydia infection is the most common sexually transmitted disease, responsible for about 2.8 million cases a year in the US. Untreated Chlamydia infections can ascend into the upper reproductive tract causing scarring and fibrosis that result in infertility and ectopic pregnancies. Similarly, systemic sclerosis (scleroderma or SSc) is a rheumatologic illness characterized by progressive scarring and fibrosis of the skin and visceral organs.
Fibrosis is a major contributor to scarring and infertility caused by Chlamydia infection, as well as the disease manifestations of systemic sclerosis (SSc). It is conventionally known that T cells, and specifically CD8 T cells, are the predominant inflammatory infiltrate in affected tissue and are thought to produce cytokines that drive the synthesis of extracellular matrix proteins by fibroblasts, resulting in excess fibrosis. Research in the mouse model for Chlamydia genital tract infections has shown unambiguously that scarring and infertility are mediated by CD8 T cells. Perhaps more specifically, the inventor hereof has shown in the mouse model that the CD8 T cell response to Chlamydia genital tract infections is atypical and includes antigen-specific CD8 T cells that produce IL-13 and tumor necrosis factor alpha (TNF-alpha) when activated; hence forth referred to herein as CD8IL-13 T cells. Similarly, in SSc, progressive scarring and fibrosis have been attributed to CD8IL-13 T cells (Fushiotti et al, 2009, Arthritis Rheum 60: 1119-28). For example, patients with SSc have enhanced numbers of CD8 T cells that produce IL-13 when activated and T cells producing IL-13 are visible in SSc skin lesions. Furthermore, activated CD8 T cells from SSc patients cause human dermal fibroblasts to express collagen and fibrinogen. The SSc CD8 T cell-driven dermal fibroblast product of scarring proteins is blocked by neutralization of IL-13, thereby directly tying the CD8IL-13 T cell subset to the immunopathology underlying SSc (Fuschiotti et al, 2013, Arthritis Rheum 65: 236-46).
Although human CD8+ T cells expressing IL-13 have been described in humans, they unfortunately do not represent a usable tool to study the biology, protein and gene expression in these cells, or to screen prospective therapeutics. This is in large part because the available human CD8IL-13 T cell subset biomarkers do not allow for the practicable purification of CD8IL-13 T cells as is required to perform the genomic and functional studies needed to develop improved diagnostic tests, test therapeutic drugs, and identify new therapeutic targets.
Accordingly, and especially given the huge impact that both Chlamydia infections and SSc have on human health and the problems that exist with currently available treatments for both conditions, there is a pressing need for an increased understanding of the role and of CD8 T cells in the human immune system and, more specifically, for a useful tool to study CD8IL-13 T cells. Similarly, a need exists to identify viable biomarkers for human CD8IL-13 T cells, with such biomarkers capable of practicable purification such that genomic and functional studies may be performed thereon. In this manner, meaningful diagnostic testing and therapeutic interventions could be screened for the purposes of (a) vaccine development, (b) diagnosing and treating pathological scarring during Chlamydia-infections, and (c) diagnosing and treating pathological scarring in patients with SSc. As provided herein, gene expression microarray experiments utilizing murine CD8IL-13 and conventional CD8 T cell clones have been used to identify candidate biomarkers for human CD8IL-13 T cells. The inventor of this application has identified that the human homolog (C10orf128) of the murine cell surface biomarker for CD8IL-13 T cells (1810011H11Rik) is expressed in the circulating CD8 T cell pool of patients with SSc and can be practicably used to purify the desired T cell subset from the peripheral blood of human subjects.